Moshe Ornstein, MD, MA: To close the loop on the I/O [immuno-oncology]–TKI [tyrosine kinase inhibitor] regimens that we’ll be discussing is the CheckMate 9ER trial (NCT03141177) of nivolumab plus cabozantinib in the frontline setting. [This trial had] similar key inclusion criteria, untreated advanced or metastatic RCC [renal cell carcinoma] with the clear cell component. Similar to the KEYNOTE-426 [clinical trial (NCT02853331)], this included all risk, and the primary end point was progression-free survival [PFS]. Patients were randomized to receive nivolumab at 240 mg IV [intravenously] every 2 weeks plus cabozantinib at 40 mg once daily vs the same standard of care of sunitinib that we’ve seen in the other trials. I’d like to highlight that the cabozantinib was at 40 mg. When cabozantinib is given in the refractory setting as a monotherapy, it’s given at 60 mg. In combination in the trial, the dose selected was 40 mg. The primary end point was progression-free survival. The secondary end points were overall survival [OS], response rates, and safety.

The baseline characteristics were very similar among the 2 arms. The IMDC [International Metastatic RCC Database Consortium] prognostic score was closer to 20% for favorable risks. In the KEYNOTE-426 trial, we saw 31% favorable risk, approximately 60% intermediate risk, and around 20% in both arms in terms of poor risk. That’s more of what we might expect in the average metastatic RCC clinic. Otherwise, the most common sites of metastases were what one would expect in this population, and the rest of the baseline characteristics were well balanced between the arms.

Let’s look at the top-line data in terms of progression-free survival and overall survival in the ITT [intention-to-treat] population. The median PFS was 16.6 months in the combination vs 8.3 months in the sunitinib arm. The median OS was superior in the combination arm compared with sunitinib, with a hazard ratio of about 0.7. As we see more of these follow-up data for the I/O-TKIs, that’s where we’re seeing the ITT hazard ratio for survival level out a bit, which is at approximately 0.7.

I’d like to highlight the response rates: 56% for the combination vs 28% for sunitinib. CR [complete response] rates with extended follow-up were 12% in the combination arm and 5% in the sunitinib arm. The primary disease progression rate was 5.6% in patients receiving cabozantinib and nivolumab. To remind you, although it was 5.6% in this study, it was approximately 11% in patients receiving axitinib and pembrolizumab. Some were in the 4% to 5% range in patients receiving lenvatinib and pembrolizumab on the CLEAR trial (NCT02811861).

[Let’s look at the] safety summary. Once again, it isn’t surprising. We’re seeing high rates of grade 1 to 2 toxicities. We’re seeing toxicities that one would expect from a TKI monotherapy in terms of diarrhea, hand-foot syndrome, hypertension, fatigue, etc. We’re also seeing toxicities that one would expect from I/O and TKIs, which can be diarrhea, fatigue, and hypothyroidism. But I don’t see anything that jumped out in this trial as an unusual toxicity in either the sunitinib monotherapy arm or the treatment arm of nivolumab and cabozantinib.

In summary, in all risks and in the ITT population, there was superiority in terms of OS, PFS, and response rates. It set a standard, or was at least another approved combination, an option for patients with treatment-naive metastatic clear cell RCC.

Transcript edited for clarity.